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This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors. Plain Language Summary: Outcomes after switching to second line antiretroviral regimens in the Thai National Treatment program We assessed the rates of virological failure, losses to follow-up and death in 29,015 people who switched to second line antiretroviral therapy in Thailand. The cumulative rate of virological failure was a 9.8% at 6 years, loss to follow-up occurred in 18.3% (5% who remained alive) and 15.9% died. Women and those with lower CD4 counts at switch had the highest risk of virological failure. [ABSTRACT FROM AUTHOR]

Introduction: A change in terminology from fatty liver disease to metabolic‐associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. Methods: We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10‐year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non‐alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan‐aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. Results: The median age was 54 years (interquartile range [IQR] 52–60) and current CD4 count was 613 (IQR 467–804) cells/mm3. A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non‐alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6–6.6), and similar associations were also observed among different MAFLD categories. Conclusions: The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals is well recognized but prospective data on predictors and subsequent outcome are limited. Methods The Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV-active HAART including lamivudine and/or tenofovir in antiretroviral naïve HIV-HBV individuals in Thailand. Results Early HF (EHF) was defined as ALT > 5 × ULN during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation, however one subject with underlying cirrhosis died following rapid hepatic decompensation. EHF was significantly associated with higher baseline ALT (79 IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log10 c/ml vs 8.4 log10 c/ml non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in 75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF cases versus 4% of non-EHF (p = 0.053). Conclusion EHF after HBV active HAART initiation was frequently observed in this population. Timing of EHF, association with elevated ALT and HBV DNA and high rate of seroconversion are all consistent with immune restoration as the likely underlying process. Clinical Trial number NCT00192595.

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients' baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART. [ABSTRACT FROM AUTHOR]

Older adults face physiological, psychological, social, and economic changes, which may impair nutritional status, making the body vulnerable to illness and adverse clinical outcomes. Little is known regarding the nutritional status among elderly people living with HIV (PLHIV). We aimed to study the prevalence of malnutrition and the associated factors in a Thai aging cohort. A cross-sectional study was conducted among PLHIV >50 years of age on long-term antiretroviral therapy and HIV-negative controls, frequency matched by sex and age in Bangkok, Thailand. Nutritional status was assessed by the Mini Nutrition Assessment (MNA) tool. Abnormal nutritional status was defined as MNA score <24 (malnutrition and at risk of malnutrition). Body composition was measured by bioelectrical impedance analysis using Body Composition Analyzer. Demographic and disease-related factors were assessed for their association with abnormal nutrition status using multivariable logistic regression. There were 349 PLHIV and 103 HIV-uninfected controls, with median age 55 years. The majority were male (63%) with median body mass index (BMI) of 23.4 kg/m2. PLHIV had lower BMI [median, 23.1 (IQR, 20.8–25.2) vs. 25.3 (22.3–28.7) kg/m2, p < .001], lower fat percent [22.8% vs. 26.3%, p < .001] and lower fat mass [14.2 vs. 16.9 kg, p < .001] and higher abnormal nutritional status (18.05% vs. 6.8%, p = .005) than controls. In the multivariate model, older age (adjusted odds ratio [aOR], 1.06, 95% confident interval [CI]: 1.01–1.12, p = .03), positive HIV status (aOR, 2.67, 95% CI: 1.07–6.65, p = .036), diabetes mellitus (aOR, 2.21, 95% CI: 1.003–4.87, p = .049), lower fat mass (aOR, 0.70, 95%CI: 0.57–0.86, p < .001), and lower BMI (aOR, 0.63, 95% CI: 0.51–0.78, p < .001) were independently associated with abnormal nutritional status. PLHIV had higher risks for abnormal nutritional status compared with HIV-uninfected individuals. Regular screening and monitoring of nutritional status among PLHIV may promote better health outcomes. [ABSTRACT FROM AUTHOR]

Background: Mental health and substance use disorders are common among people living with HIV and are associated with high-risk sexual behaviors, such as unprotected sex and multiple sexual partners, but Asia-Pacific data are limited. Methods: Adults living with HIV in care at 5 Asia-Pacific HIV clinics were enrolled at routine clinic visits between July 2019 and June 2020. Depression, substance use, sexual practice, and sociodemographic data were collected using the Patient Health Questionnaire-9, Alcohol, Smoking, and Substance Involvement Screening Test, and a study-specific questionnaire. Clinical data were accessed from medical records. Risk factors for medium-to high-risk sexual practices, defined based on total scores from the sexual practice questionnaire assessing number of sexual partners and condom use, were analyzed using logistic regression. Moderate-to-severe depression was defined as a Patient Health Questionnaire-9 score >9 and moderate- to high-risk substance use as an Alcohol, Smoking, and Substance Involvement Screening Test score ≥11 for alcohol or ≥4 for other substances. Results: Among 723 participants, the median age was 38 years, 89% were men, 99% were on antiretroviral therapy and 37% had medium- to high-risk sexual practices. Medium- to high-risk sexual practices were more common among those ≤30 years old, unemployed, and those with HIV status disclosed and were more likely in participants with moderate-to-severe depression (aOR 2.09, 95% CI: 1.17 to 3.74) compared with none-to-minimal depression, and moderate- to high-risk substance use (aOR 1.73, 95% CI: 1.23 to 2.44) compared with those without. Conclusions: Further integration of comprehensive sexual risk reduction strategies, mental health services, and substance use harm reduction within HIV clinical settings in the region is needed. [ABSTRACT FROM AUTHOR]

Objectives: Ensuring that medicines meet quality standards is mandatory for ensuring safety and efficacy. There have been occasional reports of substandard generic medicines, especially in resource-limiting settings where policies to control quality may be less rigorous. As HIV treatment in Thailand depends mostly on affordable generic antiretrovirals (ARV), we performed quality assurance testing of several generic ARV available from different sources in Thailand and a source from Vietnam. Methods: We sampled Tenofovir 300mg, Efavirenz 600mg and Lopinavir/ritonavir 200/50mg from 10 primary hospitals randomly selected from those participating in the National AIDS Program, 2 non-government organization ARV clinics, and 3 private drug stores. Quality of ARV was analyzed by blinded investigators at the Faculty of Pharmaceutical Science, Chulalongkorn University. The analysis included an identification test for drug molecules, a chemical composition assay to quantitate the active ingredients, a uniformity of mass test and a dissolution test to assess in-vitro drug release. Comparisons were made against the standards described in the WHO international pharmacopeia. Results: A total of 42 batches of ARV from 15 sources were sampled from January–March 2015. Among those generics, 23, 17, 1, and 1 were Thai-made, Indian-made, Vietnamese-made and Chinese-made, respectively. All sampled products, regardless of manufacturers or sources, met the International Pharmacopeia standards for composition assay, mass uniformity and dissolution. Although local regulations restrict ARV supply to hospitals and clinics, samples of ARV could be bought from private drug stores even without formal prescription. Conclusion: Sampled generic ARVs distributed within Thailand and 1 Vietnamese pharmacy showed consistent quality. However some products were illegally supplied without prescription, highlighting the importance of dispensing ARV for treatment or prevention in facilities where continuity along the HIV treatment and care cascade is available. [ABSTRACT FROM AUTHOR]

Introduction: Etravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens. Methods: Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database. Results: 1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01). Conclusion: The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen. [ABSTRACT FROM AUTHOR]

The 18th Bangkok International Symposium on HIV Medicine, Queen Sirikit National Convention Centre, Bangkok, Thailand, 13-15 January 2016 Consistent with HIV-NAT's mission, quality training is provided to many professional healthcare workers in the region by taking the latest knowledge from research and presenting it locally at the Bangkok International Symposium of HIV Medicine. The symposium is offered every third week of January for 3 days. Some of the plenary session content is presented below. [ABSTRACT FROM AUTHOR]

The 17th Bangkok International Symposium on HIV Medicine, Queen Sirikit National Convention Centre, Bangkok, Thailand, 14-16 January 2015 HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)'s commitment to provide educational training every January to the region returned this year after the cancellation of 2014′s symposium due to political unrest. More than 500 participants from five continents attended the 3-whole-day symposium; 60 also attended Data Safety and Monitoring Board (DSMB) preconference workshop sponsored by Harvard University's Multiregional Clinical Trial Center and 50 attended the Qualitative Research preconference workshop held by our sister organization SEARCH. A wide number of topics were discussed and a few are listed: prevention and cure, combination of antiretroviral therapy, elderly, coinfections, policy implementation, sexual health and stigma. This article briefly summarizes some of the plenary sessions. [ABSTRACT FROM AUTHOR]

Asia is seeing a rise in noncommunicable diseases in their general population and among people living with HIV. Many Asians have low body weight, which can lead to higher plasma concentrations of antiretrovirals and, as a result, their toxicities. Examples are metabolic complications from protease inhibitors, chronic kidney disease from tenofovir, and hepatotoxicity from nevirapine. Asia has not only the highest burden of hepatitis B viral infection than any other continent but also a predominance of genotypes B and C, the latter associated with higher risk for hepatocellular carcinoma. HIV-associated neurocognitive disorders are equally common among Asians as other populations. Diastolic dysfunction and asymptomatic myocardial ischemia are not infrequent. Non-Hodgkin lymphoma is the most common AIDS-related cancer, whereas Kaposi sarcoma is relatively infrequent. Emerging data show high prevalence of human papillomavirus-associated anal dysplasia in men who have sex with men. Resource-limited countries in Asia suffer from lack of resources for national screening programs of noncommunicable diseases, which, in turn, limits the epidemiologic data that exist to guide the use of national health resources. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Linkage studies have reported high rates of previously unascertained mortality among people living with HIV (PLHIV) who have been lost to follow-up (LTFU). We assessed survival outcomes among PLHIV who were LTFU in Thailand and Malaysia, through linkages to a national death registry or HIV database. Methods: Data linkages with the national death registry or national HIV database were conducted in 2020 on all PLHIV who met LTFU criteria while enrolled in care at participating HIV clinical sites. LTFU was defined as having no documented clinical contact in the previous year, excluding transfers and deaths. Survival time was analyzed using the Cox regression, stratified by site. Results: Data linkages were performed for 489 PLHIV who had been LTFU at sites in Malaysia (n = 2) and Thailand (n = 4). There were 151 (31%) deaths after being LTFU; the mortality rate was 4.89 per 100 person-years. Risk factors for mortality after being LTFU were older age [41–50 years: hazard ratio (HR) = 1.99, 95% confidence interval (CI): 1.08 to 3.68; and older than 50 years: HR = 4.93, 95% CI: 2.63 to 9.22; vs. age 30 years or younger]; receiving NRTI + PI (HR = 1.87, 95% CI: 1.22 to 2.85 vs. NRTI + NNRTI); positive hepatitis C antibody (HR = 2.25, 95% CI: 1.40 to 3.62); and having previous AIDS illness (HR = 1.45, 95% CI: 1.03 to 2.05). An improved survival was seen with a higher CD4 count (CD4 351–500 cells/µL: HR = 0.40, 95%CI: 0.21–0.76; and CD4 >500 cells/µL: HR = 0.43, 95%CI: 0.25–0.75; vs. CD4 ≤200 cells/µL). Conclusions: Almost one-third of PLHIV who were LTFU in this cohort had died while out of care, emphasizing the importance of efforts to reengage PLHIV after they have been LTFU and ensure they have access to ongoing ART. [ABSTRACT FROM AUTHOR]

Introduction: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. Methods: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. Results: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person‐years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow‐up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co‐infection, TB diagnosis, HIV VL, CD4 count and BMI. Conclusions: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Objective: To assess recent trends in the monitoring of antiretroviral therapy (ART) and detection of ART failure in adult and pediatric HIV clinics. Methods: We used data collected from 21 adult and 17 pediatric sites (across 13 and 6 countries/territories, respectively) in the International Epidemiology Databases to Evaluate AIDS - Asia-Pacific cohort. ART failure was defined as viral, immune, or clinical consistent with WHO guidelines. Results: A total of 8567 adults and 6149 children contributed data. Frequency of CD4 count monitoring declined between 2010 and 2019 among adult sites (from 1.93 to 1.06 tests/person per year, a 45.1% decline) and pediatric sites (from 2.16 to 0.86 testsperson per year, a 60.2% decline), whereas rates of viral load monitoring remained relatively stable. The proportion of adult and pediatric treatment failure detected as immune failure declined (from 73.4% to 50.0% and from 45.8% to 23.1%, respectively), whereas the proportion of failure detected as viral failure increased (from 7.8% to 25.0% and from 45.8% to 76.9%, respectively). The proportion of ART failure detected as clinical failure remained stable among adult and pediatric sites. The largest shifts in ART monitoring and failure type occurred in lower middle-income countries. Conclusions: Although viral failure in our Asian cohort now comprises a larger portion of ART failure than in prior years, the diagnostic characteristics of immune and clinical failure, and recommendations on their management, remain important inclusions for regional ART guidelines. [ABSTRACT FROM AUTHOR]

Objectives: Prevalence of cardiovascular disease increases with age. Little is known about the prevalence and risk factors for echocardiographic abnormalities among older people living with HIV (PLHIV) from Asia. Design: A cross-sectional study was conducted among PLHIV aged >50 years (N = 298) on antiretroviral treatment (ART) and HIVnegative controls (N = 100) frequency matched by sex and age in Thailand. Methods: All participants underwent standard 2-dimensional transthoracic echocardiography performed by trained cardiologists who were blinded to the participant's care and HIV status. Logistic regression was used to examine the association between cardiac abnormalities and risk factors. Results: The median age was 54.7 years (60.8% men) with 37.2% having hypertension and 16.6% having diabetes mellitus. PLHIV was on ART for a median of 16.2 years with current CD4 cell counts of 616 cells per cubic millimeter. Echocardiogram abnormalities did not differ among PLHIV (55%) and the controls (60%). The major abnormalities in PLHIV were following: left ventricular (LV) hypertrophy: 37% men and 42.2% women, LV systolic dysfunction (0.7%), diastolic dysfunction (24.2%), and pulmonary hypertension (3.9%). From the multivariate analyses in PLHIV, being aged >60 years was independently associated with diastolic dysfunction, whereas female sex and left atrial volume index of >34 mL/m² were associated with pulmonary hypertension (P < 0.05). None of the ART was significantly associated with any major echocardiographic abnormalities. Conclusions: In this long-term, well-suppressed, older, Asian PLHIV cohort, the prevalence of asymptomatic LV systolic dysfunction and pulmonary hypertension were relatively low, whereas the diastolic dysfunction and LV hypertrophy were common. Echocardiographic findings did not differ between PLHIV and HIV-uninfected controls. [ABSTRACT FROM AUTHOR]